(추인성)13.hwp

Size: px

Start display at page:

Download "(추인성)13.hwp"

종박 도
5 years ago
Views:

1 원저접수번호 :09-029(2 차 -0710) 조선대학교의학전문대학원신경과학교실 Determinants of Central Nervous System Involvement in Herpes Zoster In Sung Choo, MD, Man Young Kim, MD, Ji Yeon Chung, MD, Uk Hur, MD, Jin Ho Kim, MD, Hoo Won Kim, MD Department of Neurology, Chosun University School of Medicine, Gwangju, Korea Background: Herpes zoster is a viral disease characterized by a painful skin rash with blisters in a limited area on one side of the body, often in a stripe. Central nervous system(cns) involvements are uncommon complications of herpes zoster. The exact mechanism and risk factors are still unknown. Methods: We retrospectively reviewed the clinical data of patients who was admitted at our hospital due to herpes zoster from 2003 to The patients under age 15, herpes zoster infection without skin lesions, and cases not confirmed by a dermatologist were excluded. CNS involvements are defined as meningitis, encephalitis, single or multiple cranial neuropathies and all cases were evaluated with brain magnetic resonance imaging, spinal tapping, serological tests and confirmed by a neurologist. We compared the herpes zoster patients with CNS involvement to those without CNS involvement. Age, sex, body mass index, associated chronic medical illnesses, site and extent of skin lesion and development of post herpetic neuralgia were compared between two groups. Results: Total 1,131 subjects (male 460, female 671) were recruited. A group with CNS involvement was 91(8.04%). Sex, body mass index, associated chronic medical illnesses, extent of skin lesion were not different between two groups. A group with CNS involvement showed younger age(p<0.01), more facial and cervical skin lesions(p<0.01), lesser development of post herpetic neuralgia(p=0.048). Conclusions: CNS involvement is not a rare complication of herpes zoster and more frequent in patients with younger age and faciocervical zoster. J Korean Neurol Assoc 33(1):13-17, 2015 Key Words: Herpes zoster, CNS involvement, Post herpetic neuralgia 서 론 대상포진은바리셀라조스터바이러스 (varicella zoster virus; 수두대상포진바이러스, 이하대상포진바이러스 ) 에의해서유발되는피부질환으로심한통증을동반하는상당히흔한질환이다. 1 면역력의약화로인해잠복된바이러스가재활성화되면 Received December 9, 2014 Revised January 5, 2015 Accepted January 5, 2015 Address for correspondence: Hoo Won Kim, MD Department of Neurology, Chosun University School of Medicine, 365 Pilmun-daero, Dong-gu, Gwangju , Korea Tel : Fax : hoowon@chosun.ac.kr 서나타나는것으로알려져있다. 2,3 이질환이신경학적으로중요한것은신경계합병증이동반된다는점이다. 4-6 그대표적인것이대상포진후신경통 (postherpetic neuralgia) 으로환자는대상포진이후에수년이상심한통증때문에약물, 비약물적치료를받아야한다. 7 뇌막염이나뇌염, 람세이헌트증후군 (Ramsay Hunt Syndrome) 과같이중추신경계를침범하기도하며, 8,9 드물게는혈관염을동반하여뇌졸중이생기거나척수염을보이는증례들도보고되었다. 5,6 그러나이런신경계합병증의발생률및위험인자에대한연구는거의없다. 이에본저자들은피부발진을보여입원치료를했던대상포진환자들을후향적으로분석하여신경계합병증에대해미치는영향을분석해보고자하였다. J Korean Neurol Assoc Volume 33 No. 1,

2 대상과방법 1. 대상 2003년 1월 1일부터 2013년 12월 31일까지대상포진을주진단으로조선대학교병원에입원하였던환자들을대상으로하였다. 대상포진이성인에서대상포진바이러스가재활성화된것으로생각하여 15세이하의소아청소년은대상에서임의로제외하였다. 피부병변의위치에대한기술이잘되어있지않거나피부과전문의의진단이이루어지지않았던환자도제외하였다. 피부병변이나타나지않고혈청검사로대상포진바이러스중합효소연쇄반응 (polymerase chain reaction) 이나항체가양성으로나타나진단된중추신경계질환도제외하였다. 중추신경계감염의구분은뇌수막염, 뇌염, 뇌신경염증과기타로나누었다. 뇌척수액검사에서염증세포의증가와두통, 발열, 구토등의뇌막증상을보인경우를뇌수막염으로진단하였고, 의식장애나발작, 국소이상증상을보이고뇌척수액검사이상을동반하면뇌염으로, 대상포진에합당한피부발진을동반하고나타난얼굴마비, 안진과현훈, 구음장애나삼킴곤란등을보이면단발또는다발성뇌신경마비로진단하였다. 뇌신경마비와뇌수막염이동반된경우는임의로뇌신경마비군으로포함시켰다. 신경학적증상에대한신경과전문의의평가가되어있지않거나뇌자기공명영상 (magnetic resonance imaging) 과뇌척수액검사가되어있지않으면대상에서제외하였다. 뇌졸중이나척수염은피부발진이후에증상이나타나고면역혈청검사에서확인이되는경우에만대상에포함하였다. 포진후신경통은중추신경계침범증상보다는대상포진후합병증으로구분하였다. 2. 방법대상포진으로입원한환자에서중추신경계질환이동반된환자의비율을확인하여유병률조사를하였다. 각중추신경계질환의종류와그비율을확인하고피부병변의발생시기와증상의발생시기의차이를알아보고중추신경계질환들사이에차이가있는지알아보았다. 대상포진을환자를중추신경계증상이나타난군과나타나지않은군으로나누어여러임상적인소견들을비교하였다. 임상적요인들은나이, 성별, 키, 몸무게, 체질량지수, 기저질환의유무, 피부병변의위치, 피부병변의크기, 포진후신경통의유무등으로하였다. 저체중과의관련성을알아보기위해신체질량지수 18.5 이하를저체중으로정의하였다. 기저질환은면역저하의기준을명확히하기어려워계속적으로투약하고일상생활에지장을초래할수있는만성질환을대상으로하여치료받고있는당뇨병, 심부전증과심근경색증, 폐결핵과만성폐쇄성호흡기질환, 간경화와만성간염, 뇌경색과치매, 하반신마비, 만성신부전, 만성알코올중독증그리고모든종류의종양성질환을포함하였다. 피부병변의위치는머리에서가장가까운곳을기준으로안면부, 경부, 흉부, 요부, 미부로구분하였고병변의크기는안면부는삼차신경 2분절이하, 척수의경우는 3개피부분절이하의병변을보인경우는국한된 (localized) 병변, 이를초과할때는확장된 (extensive) 병변으로구분하였다. 포진후신경통의진단은퇴원이후 1개월이상지나서통증치료를 1개월이상지속적으로받았던경우로정하였다. Table 1. Comparison between zoster with and without CNS involvement Zoster without Zoster with CNS involvement CNS involvement p-value Number 1, Age 61.3± ± Sex (% of female) BMI 23.5± ± Low body weight (%, BMI<18.5) Underlying chronic illness (%) Associated with neoplasm (%) Facial skin lesion <0.01 Cervical skin lesion <0.01 Thoracic skin lesion <0.01 Lumbar skin lesion Sacral skin lesion Extent of skin lesion (%, extensive zoster) Postherpeticneuralgia (%) CNS; central nervous system, BMI; body mass index. 14 대한신경과학회지제 33 권제 1 호, 2015

3 3. 자료분석방법 SPSS version 18.0 (SPSS Inc., Chicago, IL, USA) 을이용하여두군의차이를독립 t-test와 χ 2 test로분석하였고여러인자들중중추신경계질환과동반된독립적요소를확인하기위해서로지스틱회귀분석을실시하였다. 결과 총 1,131명이등록되었다. 그중남자는 462명, 여자는 672명이었다. 중추신경계가침범된경우는뇌수막염 44명, 뇌신경마비 42명, 뇌수막염과뇌신경마비가동반된경우 3명, 뇌염 5명으로총 91명 (8.04%) 이었다. 전체대상포진환자의평균나이는 61.3±15.8이었고뇌수막염환자는 54.7±20.4, 뇌신경마비는 58.1±17.4, 뇌염은 74.6±20.0으로뇌수막염과뇌신경마비는더낮은연령에서, 뇌염은더높은연령에서호발하는것으로나타났다 (Table 1). 중추신경계질환의발생시기는피부병변이처음나타난시점 11일전에서 25일후까지매우다양했는데총 94명중 7명이피부병변이전에증상이나타났다. 평균시기는 3.3±4.2일이었다. 뇌신경마비는안면신경단일마비가 30명, 동안신경, 전정와 우신경, 설인신경, 미주신경등다발성뇌신경마비를보인경우가 15명이었다 (Table 2). 중추신경계질환동반군과동반하지않은군을비교하여보았을때성별, 키, 몸무게, 신체질량지수, 저체중비율, 만성질환동반여부, 종양성질환의동반여부, 피부병변의크기는서로차이가없었다. 나이는적을수록, 피부병변의위치는안면부나경부에있을경우에중추신경계질환동반이많았고, 포진후신경통은중추신경계질환동반환자에서더적게나타났다 (Table 1). 다양한인자들중독립적으로중추신경계질병발생에통계적의미가있는것으로나타난것은나이와피부병변위치, 포진후신경통발생률이었다 (Table 3). 그러나총 5명의뇌염환자들을보면, 수가적어서통계적의미를찾기는어렵지만평균나이가 74.6세로많고, 동반질환도 5명중 3명 (60%) 으로다른군에서의 30% 이하의비율에비해높은경향을보였으며, 포진후신경통은 5명중 4명으로나타나뇌수막염이나뇌신경마비와는다른양상을보였다. 고찰 대상포진바이러스는인체에병을일으키는 8종의헤르페스바이러스군중의하나로인체헤르페스바이러스타입 3으로 Table 2. Comparison among CNS involvement groups Cranial nerve palsy Meningitis Encephalitis Number Age 58.1± ± ±20.0 Sex (% of female) BMI (kg/m 2 ) 22.8± ± ±1.3 Low body weight (%, BMI<18.5) Underlying chronic illness (%) Facial skin lesion (%) Cervical skin lesion (%) Thoracic skin lesion (%) Lumbar skin lesion (%) Sacral skin lesion (%) Extent of skin lesion (% extensive zoster) Post herpetic neuralgia (%) Interval between skin lesion and onset of CNS symptoms (days) 2.9± ± ±9.6 BMI; body mass index, CNS; central nervous system. Table 3. Results of binary logistic regression analysis p-value Exp (B) 95% confidence interval of Exp (B) Lower Upper Age Facial lesion < Cervical lesion < Post herpetic neuralgia Exp; exponential. J Korean Neurol Assoc Volume 33 No. 1,

4 불리며소아에수두를일으키고성인에서대상포진을일으켜수두포진바이러스 (varicella-zoster virus) 로불리기도한다. 10,11 소아에서호흡기비말을통하거나직접접촉에의해서전파되어점막상피에피부염증을일으키고이후피부의말초신경을따라위로올라가뇌신경절, 후근신경절, 자율신경절에서잠복상태로지내다가숙주의면역계가약화될경우재활성화하여대상포진을일으키는것으로알려져있다. 12 왜면역력이약해져서바이러스의재활성이일어나는지명확하게알려져있지않지만노화, 면역억제요법, 정신적스트레스, 외상, 면역계독소등을원인으로들기도한다 재활성화되면신경세포내에서바이러스가복제되고, 형성된비리온 (virion) 들은신경축삭을타고내려가피부에염증과수포를형성한다. 심해지면근처의신경절로퍼져다른영역의피부분절로수포가확대된다 대상포진의발생률은전세계적으로비슷해서건강한청년에서천명당 1년에 명이지만 65세이상에서는 명의빈도를보이며대체적으로나이가들어가면서빈도는증가하는데이는세포성면역의기능이떨어지기때문이다 대상포진의대표적합병증은포진후신경통이다. 대상포진후수개월에서수년이상지속되는통증으로다양한약물또는중재적시술을받아야하는경우가고령, 여성, 심한발진을보인경우에서잘나타난다. 28,29 비교적흔히동반되는다른신경계합병증으로얼굴마비를동반한귀주변의대상포진을주증상으로하는람세이헌트증후군, 두통과발열, 경부경직을주증상으로하는뇌수막염이있다. 그러나피부발진을보이지않지만혈청검사나뇌척수액검사에서확진된뇌수막염이나뇌염이보고되는것으로보아신경절에서아래로내려가피부발진을일으키는기전과다르게위로올라가염증을일으키는것도가능한것같다. 4,6,30 그외에드물게보고된질환중에뇌혈관염에의한뇌졸중, 소뇌염증, 그리고급성척수병증이있다. 5,6 본저자들의연구에서는뇌졸중, 척수병증, 소뇌염은관찰할수없었고뇌수막염과얼굴마비를포함한뇌신경마비가주된동반질환이었다. 본연구에서는중추신경계질환을동반하는위험인자로상대적으로낮은연령과, 피부발진이머리에가까운얼굴이나경부에나타나는경우였다. 뇌염과는다르게뇌신경마비나뇌수막염은일반적대상포진환자보다더젊은나이에생기고, 통계적유의성은보이진않지만동반질환 (31% 와 24%) 이나종양성질환 (71.% 와 2.2%) 과의관련성도낮게나타나다른기전을가지는것같다. 또한뇌수막염이나뇌신경마비는피부발진이생기고평균 3일전후에, 뇌염의경우는 9일정도에증상이나타났다. 포진후신경통은여성, 고령, 피부병변이크고통증이심할수록더잘나타난다는보고가있지만 28 중추신경계질환의경우 엔성별이나피부병변의크기, 통증의정도와는관련이없었고피부발진의위치가중요한요소로작용하는것으로보아얼굴과목주변의신경절에서쉽게뇌막이나뇌신경으로퍼져가는것으로판단된다. 삼차신경 1분절영역의피부병변을보였던환자 16명중 14명이뇌수막염을보였고, 삼차신경 3분절을침범한 14명중뇌신경마비를보인경우가 12명으로거리와의관련이있을것으로생각된다. 뇌염의경우엔 5명중 2명은안면부병변이었고피부병변이후증상발생이 1일, 6일로빨리나타났고 3명은요추부피부분절의병변이었고증상발생기간이피부병변이생긴지 10-25일로늦게나타나거리보다는면역저하와관련이있는것으로생각된다. 본저자들의연구는임상에서비교적흔하게관찰되는대상포진의중추신경계동반질환을하나의범주로비교분석을하였다는데의의가있다고할수있다. 과거의연구들에서는뇌수막염, 뇌신경마비를드문합병증으로보는경향이있었지만저자들의연구에서최근 10여년간본병원에입원치료한대상포진환자의약 8% 에서나타나고있어서비교적흔한동반증상으로판단된다. Acknowledgement 이논문은 2011년도조선대학교학술연구비의지원을받아연구되었음. REFERENCES 1. Weinberg JM. Herpes zoster: epidemiology, natural history, and common complications. J Am Acad Dermatol 2007;57(6 Suppl):S130-S Kennedy PG. Varicella-zoster virus latency in human ganglia. Rev Med Virol 2002;12: Gilden DH, Cohrs RJ, Mahalingam R. Clinical and molecular pathogenesis of varicella virus infection. Viral Immunol 2003;16: Gilden D, Cohrs RJ, Mahalingam R, Nagel MA. Neurological disease produced by varicella zoster virus reactivation without rash. Curr Top Microbiol Immunol 2010;342: Nagel MA, Cohrs RJ, Mahalingam R, Wellish MC, Forghani B, Schiller A, et al. The varicella zoster virus vasculopathies clinical, CSF, imaging, and virologic features. Neurology 2008;70: Koskiniemi M, Piiparinen H, Rantalaiho T, Eranko P, Färkkilä M, Räihä K, et al. Acute central nervous system complications in varicella zoster virus infections. J Clin Virol 2002;25: Schmader K. Herpes zoster and postherpetic neuralgia in older adults. Clin Geriatr Med 2007;23: Miravalle AA. Ramsay Hunt Syndrome. Medscape Aug Avaliable from: URL: showall. 9. Sweeney CJ, Gilden DH. Ramsey Hunt syndrome. J Neurol Neurosurg Psychiatry 2001;71: 대한신경과학회지제 33 권제 1 호, 2015

5 10. Peterslund NA. Herpesvirus infection: an overview of the clinical manifestations. Scand J Infect Dis Suppl 1991;80: Steiner I, Kennedy PG, Pachner AR. The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 2007;6: Hope-Simpson RE. The nature of herpes zoster; a long-term study and a new hypothesis. Proc R Soc Med 1965;58: Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster? Lancet Infect Dis 2004;4: Ragozzino MW, Melton LJ 3rd, Kurland LT, Chu CP, Perry HO. Risk of cancer after herpes zoster: a population-based study. N Engl J Med 1982;307: Livengood JM. The role of stress in the development of herpes zoster and postherpetic neuralgia. Curr Rev Pain 2000;4: Schmader K, George LK, Burchett BM, Pieper CF. Racial and psychosocial risk factors for herpes zoster in the elderly. J Infect Dis 1998;178 Suppl 1:S67-S Schmader K, George LK, Burchett BM, Hamilton JD, Pieper CF. Race and stress in the incidence of herpes zoster in older adults. J Am Geriatr Soc 1998;46: Hicks LD, Cook-Norris RH, Mendoza N, Madkan V, Arora A, Tyring SK. Family history as a risk factor for herpes zoster: a case-control study. Arch Dermatol 2008;144: Kennedy PG. Key issues in varicella-zoster virus latency. J Neurovirol 2002;8: Mitchell BM, Bloom DC, Cohrs RJ, Gilden DH, Kennedy PG. Herpes simplex virus-1 and varicella-zoster virus latency in ganglia. J Neurovirol 2003;9: Arvin AM. Varicella-zoster virus. Clin Microbiol Rev 1996;9: Donahue JG, Choo PW, Manson JE, Platt R. The incidence of herpes zoster. Arch Intern Med 1995;155: Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster. Mayo Clin Proc 2007;82: Helgason S1, Petursson G, Gudmundsson S, Sigurdsson JA. Prevalence of postherpetic neuralgia after a single episode of herpes zoster: prospective study with long term follow up. BMJ 2000;321: Brisson M, Edmunds WJ, Law B, Gay NJ, Walld R, Brownell M, et al. Epidemiology of varicella zoster virus infection in Canada and the United Kingdom. Epidemiol Infect 2001;127: Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA. The incidence of herpes zoster in a United States administrative database. J Gen Intern Med 2005;20: de Melker H, Berbers G, Hahné S, Rümke H, van den Hof S, de Wit A, et al. The epidemiology of varicella and herpes zoster in The Netherlands: implications for varicella zoster virus vaccination. Vaccine 2006;24: Jung BF, Johnson RW, Griffin DR, Dworkin RH. Risk factors for postherpetic neuralgia in patients with herpes zoster. Neurology 2004;62: Kim SK, Lee SH, Choi YC, Choi IS. Neurologic complication of herpes zoster. J Korean Neurol Assoc 1994;12: Ha KS, Jeong HM, Shin DJ. Clinical correlation with CSF findings of herpes zoster. J Korean Neurol Assoc 1997;15: J Korean Neurol Assoc Volume 33 No. 1,

Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical